Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

The study protocol includes 3 visits: the screening visit and 2 postprandial metabolic studies performed in random order at an interval of 7 to 14 days, and performed with (A1) and without (A0) an intravenous (i.v.) heparin bolus followed by 250 IU/h i.v during 6 hours. Each metabolic study will last 9 hours (with 6 hours postprandial) and will include PET and stable isotopic tracer methods. At time 0, a low fat liquid meal will be ingested over 20 minutes.

Inclusion criteria

• 8 healthy LPL-deficient individuals (LPLD subjects) with history of fasting TG > 5 mmol/l and homozygote or compound heterozygote for a LPL-gene mutation;
• 8 control subjects (fasting glucose < 5.6, 2-hour post 75g OGTT glucose < 7.8 mmol/l and HbA1c < 5.8%; fasting TG < 1.5 mmol/l);
• age 18 to 75 yo;
• To be willing and able to adhere to the specifications of the protocol;
• To have signed an informed consent document indicating that they understood the purpose

Exclusion criteria

• age < 18 yo;
• overt cardiovascular disease as assessed by medical history, physical exam, and abnormal ECG
• Treatment with a fibrate, thiazolidinedione, beta-blocker or other drug known to affect lipid or carbohydrate metabolism (except statins, metformin, and other antihypertensive agents that can be safely interrupted);
• Treatment with anti-hypertensive medication (only for LPL-deficient individuals);
• presence of liver or renal disease; uncontrolled thyroid disorder;
• previous diagnosis of heparin-induced thrombocytopenia;
• Treatment with oral anticoagulation medication or platelet aggregation inhibiting drugs;
• A history of major hemorrhagic event;
• smoking (>1 cigarette/day) and/or consumption of >2 alcoholic beverages per day;;
• Female of child-bearing potential who is pregnant, breast feeding or intends to become pregnant or pre-menopausal female with a positive serum pregnancy test at the time of enrollment.